Multiple Endocrine Neoplasia 2A

Andreas Machens, Kerstin Lorenz, Tim Brandenburg, Dagmar Führer-Sakel, Frank Weber, Henning Dralle
The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 9, September 2023, Pages e734–e742
https://doi.org/10.1210/clinem/dgad156

Abstract

Context

Early genetic association studies yielded too high risk estimates for multiple endocrine neoplasia (MEN2A), suggesting a need for extended surgery.

Objective

The objective was to delineate temporal changes in MEN2A presentation by birth cohort analyses.

Methods

Birth cohort analyses (10-year increments; ≤1950 to 2011–2020) of carriers of rearranged during transfection (RET) mutations who underwent surgery for MEN2A.

Results

Included in this study were 604 carriers (155 index, 445 nonindex, 4 additional patients), with 237 carriers harboring high-risk mutations, 165 carriers moderate-high risk mutations, and 202 carriers low–moderate risk mutations. With increasing recency of birth cohorts, there was a continual decline in index patients from 41–74% to 0% (P < .001) and of medullary thyroid cancer (MTC) from 96–100% to 0–33% (P < .001). Node metastases diminished from 62–70% to 0% (P ≤ .001; high and low–moderate risk mutations), whereas biochemical cure after thyroidectomy surged from 17–33% to 100% (P ≤ .019; high and low–moderate mutations). Surgical interventions for MEN2A-related tumors were performed increasingly earlier, causing median carrier age to fall: from 51–63 to 3–5 years at thyroidectomy (P < .001); from 46–51 to 24–25 years at first adrenalectomy (P ≤ .013; high and moderate–high risk mutations); and from 43.5–66 to 16.5–32 years at parathyroidectomy. MTC diameters were more effectively decreased from 14–32 to 1–4 mm (P ≤ 002) than pheochromocytoma diameters (nonsignificant).

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